Oncostatin M and IL-6 induce u-PA and VEGF in prostate cancer cells and correlate in vivo

Third Medical Department for Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria.
Anticancer research (Impact Factor: 1.83). 10/2011; 31(10):3273-8.
Source: PubMed


Oncostatin M (OSM) and interleukin-6 (IL-6) are growth factors for prostate cancer (PC). Vascular endothelial growth factor (VEGF) and urokinase-type plasminogen-activator (u-PA) have been implicated in tumour progression. A possible interaction between IL-6, OSM, u-PA and VEGF in PC was investigated.
Primary prostate epithelial cells (PPEC) and DU-145 PC cells were treated with IL-6 or OSM and the effects on u-PA and VEGF expression were studied. Plasma levels of IL-6, OSM, u-PA and VEGF were determined in patients with or without PC.
In DU-145 cells, OSM and IL-6 up-regulated u-PA and VEGF significantly. Higher levels of IL-6 and OSM in metastasising PC than in nonmetastasising PC and benign prostatic hyperplasia (BPH) and correlations between IL-6, OSM, u-PA and VEGF were found.
OSM and IL-6 increase u-PA and VEGF in DU-145 cells but not in PPEC and possibly, by promoting matrix degradation and angiogenesis, could play a role in the pathogenesis of prostate cancer.

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    • "IL-6 is an NF-jB-regulated pleiotropic proinflammatory mediator that signals predominantly via the JAK/ STAT pathway [39] and enables tumor growth and inhibits apoptosis in a variety of human tumors [40]. A comparison of non-metastazising pancreatic cancer, benign prostatic hyperplasia and metastasized pancreatic cancer revealed elevated levels of IL-6 in the latter, more aggressive tumor [41]. In this study, it was shown that IL-6 leads to an increased expression of urokinase plasminogen activator (uPA) and vascular endothelial growth factor (VEGF), thereby implying a crucial role of IL-6 in angiogenesis of pancreatic tumors. "
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    • "These growth factors are glycosylated signaling mitogens that specifically act on endothelial cells and have various effects, including mediating increased vascular permeability, inducing angiogenesis , vasculogenesis and endothelial cell growth, promoting cell migration, and inhibiting apoptosis as well as cell survival functions [33]. Recently, was found interaction between VEGF, IL-6, u-PA and oncostatin M in prostate cancer which is possible important for tumor neovascularization and growth [31]. Moreover, it was shown that VEGFC differentially regulates VEGFA expression in ocular and cancer cells and promotes angiogenesis via RhoA mediated pathway [32]. "
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